The general objective of Project 3 is to elucidate the mechanisms that govern the transport and utilization of O2 (VO2) by skeletal muscle and determine how these mechanisms are influenced by the aging process. Although a decreased muscle mass and reduced muscle respiratory capacity have been implicated in the age-related decrement in exercise performance, the role and importance of alterations in the O2 transport system may be of significance. O2 supply is essential for respiration and O2 availability modulates metabolism. Consequently, studies are proposed that examine skeletal muscle blood flow and metabolism across the spectrum of age in humans. A repeated measures design including arterial and venous blood samples and blood flow measurements during cycle and isolated knee-extensor exercise will provide unique insight into the effect of age on the delivery and uptake of O2 by varying the importance of central and peripheral limitations. Muscle morphometry, again on the same subjects, will afford the opportunity to link structure with function in an effort to better understand the age-related decline in metabolic capacity. As intracellular P02 is key to understanding how O2 delivery translates into effects on metabolism, will continue to utilize 1H magnetic resonance spectroscopy (MRS) of myoglobin to evaluate variations in this final step of the O2 cascade from air to tissue. Finally, a complete understanding of O2 supply and demand is impossible without a method to assess the illusive phenomenon of perfusion/V02 matching. We present exciting preliminary data which combine MR perfusion imaging and 31P chemical shift imaging to provide this information in vivo. This novel technique will initially be used to assess the influence of age and O2 availability on perfusion/V02 matching, and may ultimately produce a clinically applicable tool to assess skeletal mu7scle dysfunction. Within these broad goals we will combined animal studies theoretical analyses, biochemistry, and the study of molecular mechanisms to better understand O2 transport and utilization with aging.